Crospovidone, also referred to as polyvinylpolypyrrolidone, PVPP, crospolividone or E1202, is a highly cross-linked modification of polyvinylpyrrolidone (PVP). Crospovidone is insoluble in water, though it still absorbs water and swells very rapidly generating a swelling force. This property makes it useful as a disintegrant leading to dispersible tablets. In addition, crospovidone can have advantageous properties such as absorption of certain compounds like endotoxins that may cause diarrhea. Crospovidone has E number code E1202 and is also used as a stabilizer.
The use of crospovidone as disintegrant in formulations comprising antibiotics is well known. In dispersible tablets, the amount of disintegrant normally present is from 5-10% (w/w), in some cases amounts as low as 2% (w/w) have been reported. This disintegrant may be crospovidone but can also be other disintegrants such as starch or combinations of crospovidone and other disintegrants. For example, GB 1403584 describes a dispersible tablet comprising close to 10% (w/w) of disintegrants, namely 8% (w/w) starch and less than 1% (w/w) crospovidone. WO 92/19227 describes a dispersible tablet comprising amoxicillin and clavulanic acid and from 2.73-3.78% (w/w) crospovidone. Other disclosures of dispersible tablets comprising an antibiotic and crospovidone are WO 91/07174 (18% crospovidone), CN 101524333 (15% crospovidone), ZA 9107789 (10% crospovidone), CN 101502511 (6% crospovidone), CN 1803135 (2-5% crospovidone) and EP 578231 (1.7% crospovidone) although exact disintegration times are not unambiguously disclosed in these documents making it difficult to judge whether indeed the disclosed tablets are dispersible in acceptable periods of time such as less than two or three minutes.
IN 185249B describes an improved process for preparation of rapidly soluble powders of beta-lactam antibiotics wherein a composition comprising amoxicillin trihydrate is disclosed comprising 0.2-0.8% (w/w) of crospovidone. However this concerns a powder, not a tablet suitable for rapid disintegration.
Presence of low amounts of crospovidone in tablets is also disclosed in WO 98/35672, however this document describes granulates, sachets, conventional non-dispersible tablets, chewable tablets but not dispersible tablets, although the same document also advocates that dispersible tablets will tend to comprise a relatively higher proportion of extra-granular disintegrant, to aid the dissolution process. Similarly, low amounts of crospovidone are disclosed in US 2002/168405 and WO 00/66169 but again these document concern chewable bilayer tablets and not dispersible tablets.
Finally, U.S. Pat. No. 5,262,171 discloses tablets comprising 0.5-10% of certain designed polyvinylpolypyrrolidones with specific K-values (K-30 to K-120), however the suitability of this type of disintegrant was only shown for active pharmaceutical ingredients other than antibiotics such as β-lactam antibiotics like amoxicillin, ampicillin, cephalexin, and the like. In particular, U.S. Pat. No. 5,262,171 discloses tablets comprising acetaminophen, acetylsalicylic acid, chloramphenicol, chlorpromazine, hydrochlorothiazide, methyl paraben, sulfathiazole and trimethoprim. Given the fact that these active pharmaceutical ingredients are different in chemical and physical behavior compared to the β-lactam antibiotics, the interaction with crospovidone cannot be extrapolated or predicted otherwise, in particular in view of the vast amount of prior art advocating the opposite.
In view of the fact that there is a continuous need for antibiotic tablets with as little as auxiliary components as absolutely needed, or as much as active pharmaceutical ingredient as possible, there remains a need for improved tablets comprising an antibiotic and less disintegrant compared to what is hitherto reported in the prior art.